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胰腺癌中miRNA水平异常通过调控肿瘤相关mRNA的翻译与肿瘤进展相关联。

Abnormal levels of miRNA in pancreatic cancer are linked to tumor progression by regulating the translation of tumor-associated mRNA.

作者信息

Ding Fadian, Zhong Yun, Zhang Han, Zhang Denghan, Zheng Zhou, Zhang Xiang, Liu Guozhong, Weng Shangeng

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Fujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

出版信息

Ann Med. 2025 Dec;57(1):2541315. doi: 10.1080/07853890.2025.2541315. Epub 2025 Aug 22.

Abstract

BACKGROUND

Pancreatic cancer remains one of the most malignant tumors, characterized by limited treatment efficacy.

MAIN FINDINGS

microRNAs (miRNAs) play a crucial role in regulating the proliferation, invasion, migration, drug resistance, apoptosis, and cell cycle progression of pancreatic cancer cells by inhibiting tumor-associated proteins. Metscape analysis revealed that miRNA-targeted proteins associated with pancreatic cancer are enriched in processes such as cell proliferation, mitosis, and cell migration, and participate in multiple signaling pathways. These proteins primarily localize to classical pathways, including JAK/STAT, PI3K/AKT, and Wnt/β-catenin. Furthermore, gene mutations or abnormal alternative poly(A)denylation (APA) within miRNA-targeted regions can disrupt base pairing to the 3'-Untranslated Region (3'-UTR), thereby enhancing the translation of oncogenic mRNA translation.

FUTURE DIRECTIONS

Collectively, these findings indicate that multiple miRNAs act cooperatively to influence pancreatic cancer progression. Consequently, therapeutic strategies aimed at restoring the balance of the miRNA system are essential to disrupt the 'mRNA-oncogene' vicious cycle.

摘要

背景

胰腺癌仍然是最具恶性的肿瘤之一,其特征是治疗效果有限。

主要发现

微小RNA(miRNA)通过抑制肿瘤相关蛋白,在调节胰腺癌细胞的增殖、侵袭、迁移、耐药性、凋亡和细胞周期进程中发挥关键作用。Metscape分析显示,与胰腺癌相关的miRNA靶向蛋白在细胞增殖、有丝分裂和细胞迁移等过程中富集,并参与多种信号通路。这些蛋白主要定位于经典通路,包括JAK/STAT、PI3K/AKT和Wnt/β-连环蛋白。此外,miRNA靶向区域内的基因突变或异常可变聚腺苷酸化(APA)可破坏与3'-非翻译区(3'-UTR)的碱基配对,从而增强致癌mRNA的翻译。

未来方向

总体而言,这些发现表明多种miRNA协同作用影响胰腺癌进展。因此,旨在恢复miRNA系统平衡的治疗策略对于打破“mRNA-癌基因”恶性循环至关重要。

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